Population pharmacokinetics of vancomycin in Thai adult patients was determined by non-linear mixed-effects approach using 319 vancomycin serum concentrations from 212 patients. The data were best fitted by a two-compartment model and it was used to examine the effect of patient characteristics on the vancomycin pharmacokinetics. In the final model, there was a linear relationship between vancomycin clearance, CL (L/h), and creatinine clearance calculated by Cockcroft-Gault equation, CLCr (mL/min): CL =0.044 × CLCr. Meanwhile, volume of central compartment, V 1 (L), was linearly related with the age (years old): V 1 = 0.542 × Age. Intercompartment clearance (Q) and volume of peripheral compartment (V 2) was 6.95 L/h and 44.2 L, respectively. The interindividual variability for CL, V 1, Q, and V 2 was 35.78, 20.93, 39.50, and 57.27%, respectively. Whereas, the intraindividual variability was 4.51 mg/L. Final model then was applied to predict serum vancomycin concentrations on validation group. Predictive performance revealed a bias of −1.43 mg/L (95% CI: −5.82–2.99) and a precision of 12.2 mg/L (95% CI: −1.60–26.16). In conclusion, population pharmacokinetic of vancomycin in Thai adult patients was developed. The model could be used to create vancomycin dosage regimen in the type of patient similar with the present study.
ObjectiveThis study aimed to describe the genetic and clinical risk factors associated with phenytoin‐induced cutaneous adverse drug reactions (PHT‐induced cADRs) in Thai patients.MethodA retrospective case‐control study was conducted among 88 PHT‐ cADRs (25 SJS/TEN, 37 DRESS/DIHS and 26 MPE) compared to 70 PHT‐tolerant controls during 2008‐2017. Genotyping was performed by Taqman RT‐PCR (EPHX1 337 T > C, EPHX1 416A > G and CYP2C9*3), pyrosequencing (UGT1A1*28, UGT1A1*6) and polymerase chain reaction‐sequence‐specific oligonucleotide probe (HLA‐B). Chi‐squared test and binary logistic regression were used to identify factors associated with PHT‐cADRs.ResultsMultivariate analysis showed that HLA‐B*46:01 was significantly associated with all PHT‐induced cADRs (OR 2.341; 95% CI, 1.078‐5.084; P = .032). Age of ≥60 years showed a significant association with PHT‐induced SJS/TEN (OR 3.600; 95% CI, 1.214‐10.672; P = .021). CYP2C9*3 was almost reaching statistically associated with an increased risk of PHT‐induced SJS/TEN (OR 4.800; 95% CI, 0.960‐23.990; P = .056). While HLA‐B*56:02/04 was found to have a significant association with PHT‐induced DRESS/DIHS (OR 29.312; 95% CI, 1.213‐707.994; P = .038). Moreover, female gender and HLA‐B*40:01 were associated with an increased risk of PHT‐induced MPE at OR 5.734; 95% CI, 0.910‐58.351; P = .042 and OR 3.647; 95% CI, 1.193‐11.147; P = .023, respectively.ConclusionBoth clinical (advanced age, female gender) and genetic factors (HLA‐B*46:01, CYP2C9*3, HLA‐B*56:02/04 and HLA‐B*40:01) contributed to the risk of PHT‐induced cADRs. Further studies with larger sample size may be warranted to confirm these findings and also the influence of EPHX1 gene.
We aimed to compare effectiveness and safety of the non‐vitamin K antagonist oral anticoagulants (NOACs) vs. warfarin for stroke prevention in nonvalvular atrial fibrillation (NVAF) in a developing country where anticoagulation control with warfarin is suboptimal. A real‐world study was conducted among patients with NVAF in Thailand receiving NOACs and warfarin from 9 hospitals during January 2012 to April 2018. Propensity‐score weighting was used to balance covariates across study groups. Cox regression models were used to compare the risk of thromboembolism, major bleeding, and net adverse clinical events across matched cohorts. A total of 2,055 patients; 605, 604, 441, and 405 patients receiving warfarin, rivaroxaban, dabigatran, and apixaban, respectively, were included. Median (interquartile range) time in therapeutic range (TTR) for warfarin users was 49.5% (26.6%–70.3%). Compared with warfarin, NOACs were associated with a significant reduction in major bleeding either when analyzed as a group (adjusted hazard ratio (HR) (95% confidence interval (CI)) of 0.46 (0.34–0.62) or by each agent. Compared with warfarin users with poor TTR, apixaban (adjusted HR 0.48, 95% CI 0.26–0.86, P = 0.013) and dabigatran (adjusted HR 0.44, 95% CI 0.21–0.90, P = 0.025) were associated with a lower risk of thromboembolism, in addition to markedly lower risk of major bleeding. In a healthcare system where anticoagulation control with warfarin is suboptimal, use of NOACs was associated with a profound reduction in major bleeding. The effectiveness and safety advantages of NOACs were more pronounced compared with warfarin users with low TTR.
A simple high performance liquid chromatographic method with ultraviolet detection at 229 nm is described for quantitation of amoxycillin in plasma. After deproteination of plasma samples with perchloric acid and adjustment of the pH to 4.9, the supernatant was injected onto a reversed phase C18 column, using acetonitrile:phosphate buffer (0.01 M, pH 7.4) (1:25 v/v) as the mobile phase. Amoxycillin and the internal standard, cefadroxil, were eluted at 23 min and 12 min, respectively, without interference from endogenous substances. Processed samples were stable for at least 24 h at room temperature which permitted automated batch processing overnight. Calibration plots of the amoxycillin to cefadroxil peak-height ratio vs. amoxycillin concentration were linear (P < 0.0001; r > or = 0.995) from 0.25 mg/L to at least 16.0 mg/L. Between-day and within-day imprecision (CV) ranged between 3.7% and 17.7%. Absolute recovery for amoxycillin and cefadroxil exceeded 82%. The application was demonstrated by the analysis of amoxycillin in human plasma after a single oral dose of amoxycillin (250 mg) suspension.
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